A cross‐sectional assessment of injection of “salts” and HIV transmission‐related behaviours among a cohort of people who inject drugs in Kyrgyzstan

Abstract Introduction Despite the increasing availability of new psychoactive substances (hereafter referred to as “salts”) in Eastern Europe and Central Asia, there is a dearth of epidemiological data on the relationship between injecting “salts” and HIV risk behaviours. This is particularly relevant in settings where injection drug use accounts for a substantial proportion of the HIV burden, such as in Kyrgyzstan, a former Soviet Republic. This study assessed whether injecting “salts” is associated with sexual and injection‐related HIV risk behaviours among people who inject drugs in Kyrgyzstan. Methods The Kyrgyzstan InterSectional Stigma Study is a cohort of people who inject drugs in Kyrgyzstan's capital of Bishkek and the surrounding rural administrative division of Chuy Oblast. We conducted a cross‐sectional analysis using survey data collected from cohort participants between July and November 2021, which included information on injection drug use (including “salts”) and HIV risk behaviours. To minimize confounding by measured covariates, we used inverse‐probability‐weighted logistic and Poisson regression models to estimate associations between recent “salt” injection and HIV risk behaviours. Results Of 181 participants included in the analysis (80.7% men, 19.3% women), the mean age was 40.1 years (standard deviation [SD] = 8.8), and 22% (n = 39) reported that they had injected “salts” in the past 6 months. Among people who injected “salts,” 72% (n = 28) were men, and most were ethnically Russian 59% (n = 23), with a mean age of 34.6 (SD = 9.6). Injecting “salts” was significantly associated with a greater number of injections per day (adjusted relative risk [aRR] = 1.59, 95% confidence interval [CI] = 1.30−1.95) but lower odds of using syringe service programmes in the past 6 months (adjusted odds ratio [aOR] = 0.20, 95% CI = 0.12−0.32). Injecting “salts” was also significantly associated with lower odds of condomless sex in the past 6 months (aOR = 0.42, 95% CI = 0.24−0.76) and greater odds of having ever heard of pre‐exposure prophylaxis (aOR = 4.80, 95% CI = 2.61−8.83). Conclusions (PWID) people who inject drugs who inject “salts” are a potentially emergent group with increased HIV acquisition risk in Kyrgyzstan. Targeted outreach bundled with comprehensive harm reduction and pre‐exposure prophylaxis services are needed to prevent transmission of HIV and other blood‐borne viruses.


I N T R O D U C T I O N
For more than three decades, injection drug use has fuelled the HIV epidemic in Eastern Europe and Central Asia (EECA) [1,2].Kyrgyzstan's HIV epidemic, like most EECA countries, is largely concentrated among people who inject drugs, who represent one-third of the HIV burden [3,4].While HIV prevalence in the general population is low (0.2%), prevalence among people who inject drugs is 18% [4].Of concern, there has been an increasing trend towards a generalized HIV epidemic.Specifically, in 2015, the majority of people with HIV were people who inject drugs (51%) [5].Yet, by 2021, a majority of incident cases were acquired via sexual transmission, which may reflect underreported injection risk among sexual partners of men who inject drugs [6,7].In response, Kyrgyzstan implemented syringe service programmes and methadone maintenance treatment (MMT) in both community and based settings for people who inject drugs [8].
Emerging evidence indicates that regional drug markets are shifting away from opioids and towards new psychoactive substances such as synthetic cathinones, which are commonly referred to as "salts" or "bath salts" (hereafter referred to as "salts") [9].The quantity of "salts" seized in EECA countries increased substantially from 116 kg between 2005 and 2010 to 11,000 kg between 2015 and 2020 [10].Changes in drug preference have important implications for HIV prevention, especially since MMT is less effective for people with opioid use disorder who use multiple substances, including amphetamine-type stimulants and "salts" [11].Stimulant use is associated with sexual risk-taking, multiplying potential HIV transmission/acquisition risks [12].Despite the availability of harm reduction services, stimulants such as "salts" can increase injection frequency and sexual risk behaviours and are associated with HIV outbreaks among people who inject drugs in high-income countries with low HIV incidence [13][14][15][16][17].
Qualitative data from Kyrgyzstan indicate that "salts" can be obtained through online vendors and are preferred among young people who inject drugs due to their stimulant effects and among older people who inject drugs when heroin availability is low [9].Given the paucity of epidemiological data on associations between "salt" injection and HIV risk behaviours in a region where injection drug use accounts for approximately 25% of new HIV cases, we aimed to evaluate if people who inject "salts" have elevated HIV (sexual and injection) risks compared to people who inject drugs other than "salts" in Kyrgyzstan [18].

Study recruitment and enrolment procedures
We used data from the Kyrgyzstan InterSectional Stigma (KISS) cohort study.Recruitment and enrolment procedures have been described previously [19].

Statistical analysis
Descriptive statistics were calculated for continuous (means and standard deviation) and categorical measures (frequencies and proportions).We used inverse probability of treatment weights (IPTW) to balance potential confounding variables between participants who injected "salts" and participants who did not before comparing outcomes between these exposure groups.These methods addressed concerns about potential selection bias resulting from the different recruitment methodologies.Further, since our focus was solely on the association between salt use and HIV risk behaviours, using IPTW avoided presenting associations with nuisance variables.When modelling a rare outcome, weighting to control for confounding can facilitate model convergence and reduce bias due to overfitting compared to traditional covariate adjustment [20][21][22].
Calculating each participant's IPTW was a two-step process.First, we used logistic regression to regress the exposure on the contemporaneously measured covariates listed above, then used the fitted exposure model to derive the estimated propensity score (i.e.probability of each participants' reported exposure level conditional on their measured covariates).Second, we calculated each participant's IPTW as the inverse (or reciprocal) of their estimated propensity score.The application of these weights is intended to create a pseudo-population in which potential confounders (i.e. the covariates included in the exposure model) are statistically independent of "salt" injection status [23].We calculated standardized differences to determine if weighting improved the balance of potential confounders between treatment groups "salts" injection versus no "salts" injection in the past 6 months [24,25].Standardized differences of |>0.20| were taken to indicate a meaningful imbalance in the corresponding covariates between treatment groups.Within the weighted sample, we estimated associations between "salts" injection on binary outcomes as odds ratios (OR) with 95% confidence interval (CI) using logistic regression and on count-based outcomes as relative risk (RR) with 95% CI using Poisson regression.Confounders with standardized differences |>0.20| were added as covariates to the weighted regression models.To account for the familywise error rate in multiple comparisons, we applied the Holm−Bonferroni correction to all p-values [26].All analyses were conducted using SPSS (28.01.0) and R (4.2.1).p-Values <0.05 were considered statistically significant.

R E S U LT S
Of 181 participants included in the analysis, 22% (n = 39) reported that they had injected "salts" in the past 6 months (Table 1).Among people who injected "salts," 72% (n = 28) were men, and most were ethnically Russian 59% (n = 23), with a mean age of 34.6 (SD = 9.6).Overall, weighting helped balance covariates between exposure groups; however, ethnicity, HIV status and polysubstance use remained imbalanced between treatment groups post-weighting (corresponding standardized differences |>0.20|).
In the weighted models and after adjustment for confounders (Table 2), injecting "salts" was significantly associated with a greater number of injections per day (adjusted RR [aRR] = 1.59, 95% CI = 1.30−1.95)and lower odds of having injected drugs with a used needle (adjusted OR [aOR] = 0.38, 95% CI = 0.18, 0.83).Injecting "salts" was associated Weights included age, sex at birth, city of recruitment, ethnicity, education, past 6-month unstable housing, lifetime history of incarceration, baseline HIV status, age at first injection, past 6-month injection of two or more drugs and past 6-month non-fatal overdose.Due to residual imbalances post-weighting (i.e.standardized difference >.2), fitted weighted regression models additionally adjusted for the following variables as covariates: HIV status, ethnicity and past 6-month injection of two or more drugs.Abbreviations: aOR, adjusted odds ratio; aRR, adjusted relative risk; CI, confidence interval; IDU, injection drug use; MMT, methadone maintenance treatment; PrEP, pre-exposure prophylaxis; SSP, syringe service programme.a Retained statistical significance after applying Holm−Bonferroni correction for multiple comparisons.

D I S C U S S I O N
Overall, we found significant differences that help to build an epidemiological profile of people who inject "salts" in Kyrgyzstan.This profile suggests that on average, people who injected "salts" were significantly younger, more likely to be recently unstably housed but less likely to have ever been incarcerated compared to people who did not inject "salts."This underscores the potential for HIV transmission via injection and sexual risk behaviours in this population.
Despite injecting more frequently, participants who injected "salts" were significantly less likely to have accessed SSPs for sterile syringes in the past 6 months compared to those who did not inject "salts" suggesting the potential for increased concern for injection-related transmission.Conversely, participants who injected "salts" were significantly less likely to report having condomless sex in the past 6 months and more likely to have heard of PrEP.While not significant in the corrected models, there was still an observed positive association with other elevated sexual risk behaviours, namely having multiple partners and exchanging sex for resources.This suggests some potential for elevated risk of sex-related transmission in this group, and underscores the need to leverage PrEP awareness campaigns to facilitate increased screening for salt use and promote evidence-based HIV prevention strategies in this population (e.g.SSP, HIV testing and PrEP linkage).These findings are consistent with qualitative data from Kyrgyzstan indicating that the short-lived stimulant effects of "salts" require more frequent injecting and are associated with increased sexual risk [9].
In 2016, only two EECA countries, Tajikistan and Estonia, met the UNAIDS recommended target of providing at least 200 needles per year per person who injects drugs [1].Previous modelling indicates that stimulant injection, including "salts," represents a substantial proportion of new HIV acquisitions, thereby necessitating greater availability of highcoverage SSPs [27].However, lower engagement in SSPs sug-gests that current services and outreach targeting people who inject "salts" in the EECA are likely inadequate.Additional research is needed to understand how SSPs can more effectively reach people who inject "salts" and identify barriers to utilizing of those services.Surveillance of drug trends is needed to inform how harm reduction services can more rapidly adapt and respond to shifting drug markets and preferences.
Our study is subject to several limitations.First, inference based on findings from a small sample should be considered exploratory.Due to the cross-sectional nature of the data, interpretation of these associations should not be considered causal.As data were collected from two sites in or near a large urban setting, findings should not be considered generalizable to all people who inject "salts" in Kyrgyzstan.Recruitment occurred during different phases of the COVID-19 pandemic, and may have affected some individuals' willingness to respond to our multi-method recruitment strategy.Finally, both exposures and outcomes were based on selfreport, which could be imprecise or underreported due to recall or social desirability.

C O N C L U S I O N S
In conclusion, "salts" injection could be an emerging threat to the HIV response in the EECA region with implications to expand harm reduction services tailored specifically to the needs of this group who may be at increased risk for HIV acquisition.

Table 1 . Sample characteristics among people who injected "salts" in the past 6 months before and after weighting
a HIV test results assessed via OraQuick™ Rapid HIV antibody test.